2026-08-29T19:28:20Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/175472024-11-29T19:03:37Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Tummala, Krishna S author Gomes, Ana L author Yilmaz, Mahmut author Graña, Osvaldo author Bakiri, Latifa author Ruppen, Isabel author Ximénez-Embún, Pilar author Sheshappanavar, Vinayata author Rodriguez-Justo, Manuel author Pisano, David G author Wagner, Erwin F author Djouder, Nabil author 2014-12-08 Molecular mechanisms responsible for hepatocellular carcinoma (HCC) remain largely unknown. Using genetically engineered mouse models, we show that hepatocyte-specific expression of unconventional prefoldin RPB5 interactor (URI) leads to a multistep process of HCC development, whereas its genetic reduction in hepatocytes protects against diethylnitrosamine (DEN)-induced HCC. URI inhibits aryl hydrocarbon (AhR)- and estrogen receptor (ER)-mediated transcription of enzymes implicated in L-tryptophan/kynurenine/nicotinamide adenine dinucleotide (NAD(+)) metabolism, thereby causing DNA damage at early stages of tumorigenesis. Restoring NAD(+) pools with nicotinamide riboside (NR) prevents DNA damage and tumor formation. Consistently, URI expression in human HCC is associated with poor survival and correlates negatively with L-tryptophan catabolism pathway. Our results suggest that boosting NAD(+) can be prophylactic or therapeutic in HCC. Cancer Cell . 2014 ;26(6):826-839. 10.1016/j.ccell.2014.10.002 1878-3686 Cancer cell 25453901 http://hdl.handle.net/20.500.12105/17547 Inhibition of de novo NAD(+) synthesis by oncogenic URI causes liver tumorigenesis through DNA damage.